Arthropod-borne viral diseases have re-emerged as major health problems in most tropical countries. For example, the incidence of dengue fever has increased greatly over the past 20 years, recently including its hemorrhagic form with associated human fatalities. The mosquito Aedes aegypti is the primary vector. In addition, A. aegypti is an excellent laboratory model for examining vector interaction with a malaria parasite (Plasmodium gallinaceum) and a lymphatic filarioid nematode (Brugia malayi). Whole genome sequence data is available for humans, Drosophila melanogaster, the malaria parasite vector Anopheles gambiae, the malaria parasite Plasmodium falciparum, and several other parasite genome projects are underway. This proposal seeks to initiate an A. aegypti genome project, with an expectation that complete knowledge of the mosquito vector, parasite and human genomes will promote and foster new disease control strategies. The immediate objectives of this project are to: (1) sequence both ends of 40,000 cDNAs derived from normalized libraries produced from 4 specific mRNA sources (from pooled mRNAs isolated from various developmental stages and adult tissues and from females exposed to infected blood meals containing dengue virus, a malaria parasite, and a filarial worm parasite), (2) to sequence both ends of 50,000 genomic DNA Bacterial Artificial Chromosome (BAC) clones, and (3) to use fluorescent in situ hybridization (FISH) technology to physically map 1000 A. aegypti BAC clones to metaphase chromosomes. These aims will develop a body of genome information including EST sequences, genomic sequences, and the physical map positions of large genomic clones that will enhance gene discovery, and also provide critical tools for an eventual complete genome sequencing project. The proposal complements a nearly completed genome project to examine the primary malaria vector, Anopheles gambiae, as the 2 species reflect the range of genome size and organization among mosquito species. The long range goal is to promote and foster collaboration between funding agencies to support an effort to sequence the entire A. aegypti genome.